Untangling the Biology of Genetic Cardiomyopathies with Pluripotent Stem Cell Disease Models

Abstract

Purpose of Review: Recently, the discovery of strategies to reprogram somatic cells into induced pluripotent stem (iPS) cells has led to a major paradigm change in developmental and stem cell biology. The application of iPS cells and their cardiac progeny has opened novel directions to study cardiomyopathies at a cellular and molecular level. This review discusses approaches currently undertaken to unravel known inherited cardiomyopathies in a dish. Recent Findings: With improved efficiency for mutation correction by genome editing, human iPS cells have now provided a platform to untangle the biology of cardiomyopathies. Multiple studies have derived pluripotent stem cells lines from patients with genetic heart diseases. The generation of cardiomyocytes from these cells lines has, for the first time, enable the study of cardiomyopathies using cardiomyocytes harboring patient-specific mutations and their corrected isogenic counterpart. The molecular analyses, functional assays, and drug tests of these lines have led to new molecular insights in the early pathophysiology of left ventricular non-compaction cardiomyopathy (LVNC), hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and others. Summary: The advent of iPS cells offers an exceptional opportunity for creating disease-specific cellular models to investigate their underlying mechanisms and to optimize future therapy through drug and toxicity screening. Thus far, the iPS cell model has improved our understanding of the genetic and molecular pathophysiology of patients with various genetic cardiomyopathies. It is hoped that the new discoveries arising from using these novel platforms for cardiomyopathy research will lead to new diagnostic and therapeutic approaches to prevent and treat these diseases.